Recurrent LDL-receptor mutation causes familial hypercholesterolaemia in South African coloureds and Afrikaners

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The use of DNA markers in the pre-clinical diagnosis of familial adenomatous polyposis in families in South Africa

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Fluorescent in situ hybridization evaluation of human Y-bearing spermatozoa separated by albumin density gradients

Objective: Fluorescent in situ hybridization of decondensed sperm nuclei was employed to evaluate the effectiveness of the Ericsson albumin gradient enrichment technique of Y-bearing sperm. Design: Mature human spermatozoa were separated from donor- and randomly selected patient semen using three different albumin density layers. Sperm nuclei, in the albumin layer with highest density, were decondensed and the percentage Y-bearing sperm was determined by fluorescent in situ hybridization. Results: A slight, although statistically significant, increase in percentage Y bearing sperm was observed. Conclusion: Although statistically significant, the clinical relevance of the small increase in Y-bearing sperm remains uncertain. A randomized controlled clinical study should help to clarify the above laboratory results.Articl

A novel deletion at codon 441 of the APC gene associated with ophthalmic lesions (CHRPE) in a South African family

A novel mutation at codon 441 in exon 10 of the adenomatous polyposis coli (APC) gene was identified in a South African family of mixed ancestry, using a convenient, non-radioactive, heteroduplex-SSCP screening assay. This single thymidine deletion after nucleotide position 1322 creates a frameshift resulting in a downstream stop codon at amino acid residue 453 of the APC gene. Genotypes of nine family members were subsequently correlated with the presence or absence of congenital hypertrophy of the retinal pigment epithelium (CHRPE), since expression of this common extracolonic manifestation of FAP is largely determined by the length of the truncated protein. CHRPE was absent in the five unaffected family members analysed, while four mutation positive subjects showed these ophthalmic lesions. Correlation between the molecular analysis and ophthalmic examinations, performed without knowledge of clinical and genetic status respectively, provided additional evidence in favour of the view that the range of phenotypic expression in FAP may result from different allelic manifestations of APC mutations.Articl

Deletion mapping of 39 random isolated Y-chromosome DNA fragments

Thirty-nine recombinants isolated from a Y chromosome-specific library were deletion mapped. Seven deletion intervals were defined by hybridization of probes to DNA of eight individuals with aberrant Y chromosomes. Extreme cytogenetic limits of the deletion intervals were determined by in situ hybridization of one probe per deletion interval. Five intervals, with a total of twenty-five probes, were allocated to the long-arm euchromatic region. The probes described will be useful for characterization of aberrant Y chromosomes, in searching for expressed sequences on the Y chromosome, and for further study of the evolutionary relationship between the Y chromosome and other chromosomes.Articl

Haplotype associations of three DNA polymorphisms at the human low density lipoprotein receptor gene locus in familial hypercholesterolaemia

The frequency and inheritance of three restriction fragment length polymorphisms (RFLPs) of the low density lipoprotein (LDL) receptor gene were investigated in 27 South African families with familial hypercholesterolaemia. Four haplotypes, defined by the enzymes PvuII, StuI, and NcoI, were found to segregate in this population. The frequency of the rare allele detected by NcoI was found to be 0.53 in 45 unrelated familial hypercholesterolaemic (FH) patients compared to 0.33 in 60 normal controls (p<0.005). In 71% of the families studied, a haplotype with common alleles for PvuII and StuI and the rare allele for NcoI cosegregated with the defective gene. In 20% of the families, a second haplotype with rare alleles for PvuII and StuI and common allele for NcoI segregated with FH. In these families the haplotypes unambiguously cosegregate with the disease and can therefore be used for early diagnosis of FH.Articl